肝细胞模拟物解毒酒精中毒。
A Hepatocyte-Mimicking Antidote for Alcohol Intoxication.
机构信息
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, USA.
Department of Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90033, USA.
出版信息
Adv Mater. 2018 May;30(22):e1707443. doi: 10.1002/adma.201707443. Epub 2018 Apr 11.
Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to remove alcohol efficiently. Upon alcohol consumption, alcohol is sequentially oxidized to acetaldehyde and acetate by the endogenous alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Inspired by the metabolism of alcohol, a hepatocyte-mimicking antidote for alcohol intoxication through the codelivery of the nanocapsules of alcohol oxidase (AOx), catalase (CAT), and aldehyde dehydrogenase (ALDH) to the liver, where AOx and CAT catalyze the oxidation of alcohol to acetaldehyde, while ALDH catalyzes the oxidation of acetaldehyde to acetate. Administered to alcohol-intoxicated mice, the antidote rapidly accumulates in the liver and enables a significant reduction of the blood alcohol concentration. Moreover, blood acetaldehyde concentration is maintained at an extremely low level, significantly contributing to liver protection. Such an antidote, which can eliminate alcohol and acetaldehyde simultaneously, holds great promise for the treatment of alcohol intoxication and poisoning and can provide therapeutic benefits.
酒精中毒会导致严重疾病，而目前的治疗方法大多是支持性的，无法有效地去除酒精。饮酒后，内源性的醇脱氢酶和醛脱氢酶分别将酒精氧化为乙醛和乙酸盐。受酒精代谢的启发，通过将酒精氧化酶（AOx）、过氧化氢酶（CAT）和醛脱氢酶（ALDH）的纳米胶囊递送至肝脏，设计了一种肝细胞模拟解毒剂来治疗酒精中毒，AOx 和 CAT 催化酒精氧化为乙醛，而 ALDH 催化乙醛氧化为乙酸盐。给酒精中毒的小鼠给药后，解毒剂迅速在肝脏中积累，并显著降低血液中的酒精浓度。此外，血液中乙醛的浓度保持在极低水平，这对肝脏保护有重要作用。这种同时消除酒精和乙醛的解毒剂有望成为治疗酒精中毒和中毒的有效方法，并能带来治疗益处。
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